Cushing syndrome (CS), a fatal disease, is suspected in many thousands of patients each year, but confirmed in only a fraction of these. This project seeks to identify accurately which patients have Cushing syndrome, to define the etiology of their disease, and to treat it optimally. A major initiative in the past year has been to examine the potential role of vasopressin in the pathogenesis of Cushing's disease. Vasopressin (VP) is known to induce ACTH secretion, and thus might stimulate corticotropes to form tumors. We measured vasopressin concentrations in the petrosal sinuses of patients with Cushing's syndrome and normal volunteers. Unexpectedly, regardless of diagnostic group, nearly all subjects showed a "dominant" petrosal sinus on basal sampling, so that one of the petrosal sinuses had greater levels of both ACTH and VP than the contralateral sinus. However, the absolute concentration of VP was greater in patients with CS than in normal volunteers, and was similar in patients with various causes of CS. Petrosal sinus VP levels in the dominant petrosal sinus increased further after CRH administration. The similarity of petrosal VP levels in CS suggests that VP is not involved in the etiology of Cushing's disease. Other studies during this reporting period focussed on diagnostic and treatment approaches for patients with adrenal masses. We examined the role of surgery in management of pheochromocytoma, demonstrating that bilateral adrenalectomy should not be performed in the setting of ACTH secretion from the tumor.